Nephrolithiasis is a condition in which one or more calculi (stones) are present in the kidneys. In addition to being present in the kidneys, these stones can also travel into the ureter (which is referred to as ureterolithiasis). Stone formation results when urine becomes supersaturated with certain poorly soluble stone-forming constituents, such as calcium, uric acid, etc. The chemical composition of a stone depends on the stone-forming constituents present in the urine. The four most common types of stones are calcium stones, uric acid stones, cystine stones and struvite stones. Calcium stones are the most common type of stones. Several different types of calcium stones are known, such as calcium oxalate stones, calcium phosphate stones and calcium oxalate and phosphate stones. Calcium stones develop as a result of hypercalciuria, metabolic or hormonal disorders (such as hyperparathyroidism and rental tubular acidosis), etc. Uric acid stones can develop as a result of a diet high in purines. Moreover, conditions such as gout and treatments such as chemotherapy can also increase the risk of uric acid stones. Cystine stones form as a result of a rare, congenital condition known as cystinuria that results in large amounts of cystine being present in the urine. Struvite stones develop when a urinary tract infection (i.e. cystitis) affects the chemical balance of the urine.
In the kidney, stones grow on the surfaces of the papillae, detach and accompany urine as it travels out of the kidney and into the ureter. Kidney stones that are very small (i.e., under four millimeters), are capable of moving through the urinary tract without any symptoms. Such stones are referred to as “silent” stones. However, larger stones, cannot be excreted and even smaller stones can become lodged in the ureter. When a stone becomes lodged in the urinary tract, it can cause irritation or blockages. When such lodging or blockage occurs, the stones cause the urinary tract to go into a spasm, a condition known as “renal colic”. Renal colic causes a severe cramping pain felt in the back and side and, sometimes, in the lower abdomen. Eventually, pain may spread to the groin. Irritation of the urinary tract often causes frequent urination. Blockages can also result in difficulty urinating. Blood in the urine, also called hematuria, is also common. In addition to renal colic, hematuria and frequent urinating, other symptoms of kidney stones include nausea, vomiting, a burning sensation while urinating, fever and/or chills.
Unfortunately, about fifteen (15) percent of men and about seven (7) percent of women will experience at least one kidney stone by age 70. In fact, kidney stones affect about 2 out of every 1,000 people per year. Recurrence is common, and the risk of recurrence is greater if two or more episodes of kidney stones have occurred. A number of drugs are used for treating patients suffering from recurring nephrolithiasis, such as thiazides (i.e. hydrochlorothiazide), potassium citrate and allopurinol (Allopurinol is well known in the art as a non-selective xanthine oxidase inhibitor that is commonly prescribed for treating gout. Allopurinol is a purine analogue and as such, its structure is similar to purines. However, allopurinol is known to inhibit a number of enzymes involved in purine/pyrimidine metabolism, such as purine nucleoside phosphorylase and orotidine-5′-monophosphate decarboxylate). The kind of drugs selected for treatment depends on the composition of the stones and on the underlying condition which caused the stone formation. However, each of these drugs causes a number of side effects. For example, the major side effect associated with thiazides is hypokalemia, which leads to reductions in urinary citrate excretion. Some patients that receive potassium citrate therapy experience gastrointestinal intolerance, especially older patients and patients with dyspepsia. Side effects caused by allopurinol include, but are not limited to, rash, hypertension, blood disorders, gastrointestinal disorders, etc. Therefore, there is a need in the art for new and improved therapeutic agents that can be used in treating patients suffering from nephrolithiasis.